The mouse and human zonae pellucidae contain homologous glycoproteins, ZP1, ZP2, ZP3. The human ZP1, ZP2 and ZP3 genes are conserved with respect to mouse Zp1, Zp2, and Zp3 and encode polypeptides of 638, 745 and 424 amino acids, respectively. A fourth zona gene (ZP4) is expressed and the protein product incorporated into the zonae pellucidae of human and rat, but not mouse eggs. Taking advantage of the observation that human sperm will not bind or fertilize mouse eggs, we have developed a genetic approach to determine which zona protein(s) are required for sperm binding. We have established transgenic mice that express each of the human zona proteins and by simple breeding experiments, plan to derive mice with chimeric zona pellucida containing one or more of the human zona proteins and test them for their ability to support human sperm binding and induction of acrosome exocytosis.